Breast and uterine cancers are both known as hormone-dependent cancer, and estrogen—a sex steroid hormone—relates closely to the development and proliferation thereof. One conventional method for the treatment of breast cancer is an endocrine therapy using an anti-estrogen drug (tamoxifen) which binds to an estrogen receptor (ER) serving as a transcriptional factor to inhibit the transcriptional activity thereof. But, this method poses a problem in that relapse occurs as a result of acquisition of drug resistance in the course of the treatment. Also, this drug has been elucidated to increase the risk of the development of uterine cancer, and problematically has severe adverse side effects. Meanwhile, in one method for the treatment of uterine cancer, progestin—a synthetic drug similar to progesterone (hormone)—is administered to subjects to inhibit the effect of estrogen on the uterus. But, this method, problematically, makes their feelings unstable and increases their body weights, for example.
In order to overcome the above-described problems in such conventional treatment methods, there is a need to reveal the mechanism of estrogen action in breast and uterine cancers and explore a new molecular target on the basis of that mechanism.
Meanwhile, the bladder is an internal organ differentiated from the genitourinary system similar to the uterus and other organs and thus, presumably, is controlled by sex hormones such as estrogen and androgen. In addition, in menopausal disorders due to estrogen deficiency, bladder disorders are likely to occur. Although the relation between bladder cancer and sex hormones has not yet been elucidated, generally, bladder cancer is known to develop in male more than in female. As conventional method for the treatment of bladder cancer, surgical total cystectomy is often performed. After total cystectomy, however, urinary tract diversion is required for all the subjects. As a result, their lifestyles must be changed in some cases, leading to deterioration in quality of life (QOL). In recent years, therefore, a bladder conservation therapy is attempted depending on the cases of interest. But, there are many cases in which an anti-cancer agent, an irradiation therapy, etc. are not effective.
In order to overcome the above-described problems in such conventional treatment methods, demand has arisen for the development of a therapy for bladder cancer which is based on a different action mechanism from conventional cases and has adverse side effects to a less extent.
Meanwhile, in recent years, many attempts have been made to apply, to a cancer therapy, a technique of RNA interference (RNAi) which can suppress the expression of a target gene in a sequence-specific manner by introducing into cells a small-molecule RNA of about 18 to about 29 bases (short interfering RNA (siRNA)). Actually, many literatures report that the proliferation of cancer cells can be inhibited using siRNA targeting the gene involved in the cancer (for example, Japanese Patent Application Laid-Open (JP-A) Nos. 2006-500916 and 2006-528618). However, in order for such RNAi technique to be applied to actual medical treatments, there is a need to develop excellent siRNA which has a high expression suppressive effect on and a high specificity to a target gene. At present, further development is demanded.